This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Core tip: Some of the targets discussed here have been discovered to enhance the effectiveness of gemcitabine upon co-administration of the corresponding agents, for instance, hyaluronidase can deplete hyaluronan in stromal region to enhance gemcitabine delivery. Besides, some signaling molecules, e.g., RalGEF-RAl, Rac1, and PAR2 are being targeted to suppress metastasis. Tumour proliferation is limited upon DR5 activated apoptosis and others promising therapeutic areas like epigenetic modifiers; IAP, miR, lncRNA, and cancer stem cells-tumour microenvironment will also be discussed.